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Biomedical subjects

M Bickel

Publications and source records attributed to M Bickel.

At least 19 recordsLinked to original sources
PubMed2006

Interleukin-1beta, interleukin-12 and interleukin-18 levels in gingival fluid and serum of patients with gingivitis and periodontitis.

INTRODUCTION: Cytokines are of major importance in periodontal disease progression. Interleukin-12 (IL-12) stimulates interferon-gamma production by T helper type 1 (Th1) cells while IL-18 induces Th1 responses when present with IL-12 but Th2 responses in the absence of IL-12. IL-1beta has been correlated with periodontal disease destruction. This study determined the local concentrations of these cytokines in sites of gingivitis and periodontitis. METHODS: Gingival crevicular fluid was collected from two sites in each of 10 gingivitis patients and from two gingivitis sites and two periodontitis sites from each of 10 periodontitis patients. Serum samples were also collected. IL-1beta, biologically active IL-12 p70, the IL-12 p40 subunit and IL-18 concentrations were determined by enzyme-linked immunoabsorbent assay. RESULTS: IL-1beta and IL-18 concentrations were higher in the gingival crevicular fluid from periodontitis patients than in that from gingivitis patients; IL-18 concentrations were higher than those of IL-1beta. Very little IL-12, either p40 or p70, was detected in the gingival crevicular fluid samples. In the serum, very low levels of cytokines were found. The level of serum IL-12 p40, however, was higher than in the fluid from periodontitis sites of periodontitis patients. CONCLUSION: The local production of IL-1beta and IL-18 in the gingival crevicular fluid increased with increasing inflammation and IL-18 was the predominant cytokine at both gingivitis and periodontitis sites. Very little IL-12 was detected with levels decreasing with increasing inflammation. These results suggest that there is an association between severity of periodontal disease and levels of IL-1, IL-12 and IL-18.

Adult↗
PubMed2006

A randomized, open-label study to compare the effects of two different doses of recombinant human growth hormone on fat reduction and fasting metabolic parameters in HIV-1-infected patients with lipodystrophy.

BACKGROUND: Several studies have shown beneficial effects of recombinant human growth hormone (r-hGH) in reducing visceral adipose tissue (VAT) in HIV-1-infected patients with lipodystrophy. METHODS: Patients were randomized to r-hGH 4 mg daily (group A) or three times per week (group B) over 12 weeks, followed by a 2 mg daily maintenance dose for 12 weeks. Magnetic resonance imaging (MRI) scans were performed to assess body composition. RESULTS: A total of 26 subjects were included in the study. VAT was reduced overall by 35.1 cm(2) (29.5%) at week 12 and by 49 cm(2) (39.9%) at week 24, respectively, compared with baseline (P<0.001 for both comparisons). By week 12, VAT was reduced by 27 and 29% (A vs B; P=0.47) while facial fat was reduced by 3.3 and 2.6 cm(2) in groups A and B, respectively (P=0.96). Over 24 weeks, VAT was reduced by 42 and 38% (P=0.35) and facial fat by 3.2 and 2.4 cm(2) in groups A and B, respectively (P=0.91), compared with baseline. There was a greater increase in high-density lipoprotein (HDL) in group A than in group B (4.9 vs 2.4 mg/dL in week 12 and 7.1 vs -0.4 mg/dL in week 24; P=0.03). Fasting insulin levels increased, whereas glucose and insulin measured in oral glucose tolerance tests remained unchanged. Drug-related side effects were transient and reversible, but more common in group A (67%) than in group B (29%). CONCLUSIONS: This study confirms reports that r-hGH effectively reduces VAT, with a relatively small reduction of facial and limb fat.

Adipose Tissue↗
PubMed2005

The Protease Inhibitor Transfer Study (PROTRA 1): abacavir and efavirenz in combination as a substitute for a protease inhibitor in heavily pretreated HIV-1-infected patients with undetectable plasma viral load.

OBJECTIVES: The aim of the study was to evaluate the safety and efficacy of abacavir (ABC) and efavirenz (EFV) instead of a protease inhibitor (PI) in HIV-1-infected subjects treated with two nucleoside reverse transcriptase inhibitors (NRTIs) and one PI with undetectable viral loads (< 50 HIV -1 RNA copies/mL). To be eligible for inclusion, patients had to have a history of viral load < 400 copies/mL for at least 3 months and had to be naive to treatment with nonnucleoside reverse transcriptase inhibitors (NNRTIs) and ABC, but multiple pretreatment and treatment failure were allowed. DESIGN: An open-label, single-centre pilot study of duration 48 weeks was conducted. ABC was added to the original treatment with two NRTIs and one PI at baseline, and at week 6 the PI was replaced by EFV. At each study visit, CD4 cell count, viral load [measured by polymerase chain reaction (PCR)] and clinical chemistry were measured. Fasting blood samples were taken at baseline and at weeks 12, 24, 36 and 48 to measure levels of cholesterol [high-density lipoprotein (HDL)/low-density lipoprotein (LDL)], triglycerides, insulin and C-peptide. Additionally, an oral glucose tolerance test (OGTT) was performed. A bioelectric impedance analysis (BIA) and a single slice abdominal and mid-thigh computed tomography (CT) scan were carried out to assess changes in body composition. RESULTS: Thirty patients were included in the study. Three patients experienced ABC-hypersensitivity and one patient demonstrated virological failure caused by nonadherence. At week 48, all remaining patients had viral loads < 50 copies/mL with stable CD4 counts. The fasting metabolic parameters and abdominal fat distribution remained unchanged. CONCLUSIONS: In heavily pretreated patients, ABC and EFV in combination provide an effective, simplified and well-tolerated alternative to PI treatment.

Adult↗
PubMed2004

Analysis of the anorectic efficacy of HMR1426 in rodents and its effects on gastric emptying in rats.

OBJECTIVES: Pharmacodynamics of HMR1426 in rodents. SUBJECTS: Male and female rats and male mice. MEASUREMENTS: 24 h feed consumption was measured. From the time curves IC(50) values of HMR1426 were calculated. Microanalysis of feeding behavior was determined. Macronutrient preference was measured, by offering rats three different diets. Gastric emptying was measured after liquid gastric loads or solid meals. In rats with gastric cannulas, milk consumption was measured with closed or open cannulas. Diabetes-related parameters and thyroid hormones were measured. RESULTS: HMR1426 inhibited feed consumption dose-dependently in rodents. Microstructural analysis of feeding after HMR1426 differed from central acting anorectics. HMR1426 inhibited consumption of fat- and carbohydrate-enriched diets. Gastric emptying was dose- and time-dependently delayed. Gastric emptying correlated with the time course of the anorectic effect. In sham-fed rats, HMR1426 had no anorectic effect with open cannulas. Anorectic effect occurred with closed cannulas. We proved that HMR1426 is not a CCK(A) agonist. CONCLUSION: The correlation between anorectic properties of HMR1426 and gastric emptying suggests that gastric emptying may cause the anorectic properties of HMR1426. The differences in microstructural feeding behavior between HMR1426 and centrally active anorectics makes it unlikely that HMR1426 acts via the CNS. Evidence for a peripheral mode of action is derived from sham-fed rats with open gastric fistula. When the milk fed was drained, HMR1426 was ineffective. HMR1426 is not a CCK(A) agonist. The molecular action of HMR1426 causing gastric emptying and its anorectic properties are under investigation.

Animals↗
PubMed2001

Durability of HIV-1 viral suppression over 3.3 years with multi-drug antiretroviral therapy in previously drug-naive individuals.

BACKGROUND: Relatively little is known about the long-term durability of viral suppression in individuals initially achieving a viral load of less than 50 copies/ml within 24 weeks of starting antiretroviral therapy, nor the extent to which therapy interruption accounts for the loss of suppression. METHODS: We intensely followed all 336 antiretroviral-naive patients attending the Goethe Universitat Clinic who began multi-drug combination regimens and in whom a viral load of less than 50 copies/ml was achieved within 24 weeks, in order to assess the risk of viral load rebound. Inspection of case notes allowed the distinction of viral rebound according to whether there was an associated complete interruption of therapy. RESULTS: A total of 61 patients experienced viral rebound during 543.1 person-years of follow-up, giving a 25.3% risk of rebound by 3.3 years from first achieving viral suppression. However, for 47 of the patients with viral rebound there was an associated documented complete interruption of antiretroviral therapy, mostly as a result of co-morbidities, leaving 14 who appear to represent a failure of the virological efficacy of therapy (viral breakthrough; 5.2% risk by 3.3 years). The risk of viral breakthrough declined with the increased duration of suppression (P = 0.01). CONCLUSION: The intrinsic virological effectiveness of multi-drug antiretroviral therapy in previously drug-naive individuals appears to be such that viral suppression, once achieved, can be maintained for several years in patients not interrupting therapy. The major challenge is to develop regimens that can be taken consistently and safely for such long periods of time.

Adult↗
PubMed2001

Discontinuation of secondary prophylaxis against Pneumocystis carinii pneumonia in patients with HIV infection who have a response to antiretroviral therapy. Eight European Study Groups.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection and a history of Pneumocystis carinii pneumonia are at high risk for relapse if they are not given secondary prophylaxis. Whether secondary prophylaxis against P. carinii pneumonia can be safely discontinued in patients who have a response to highly active antiretroviral therapy is not known. METHODS: We analyzed episodes of recurrent P. carinii pneumonia in 325 HIV-infected patients (275 men and 50 women) in eight prospective European cohorts. Between October 1996 and January 2000, these patients discontinued secondary prophylaxis during treatment with at least three anti-HIV drugs after they had at least one peripheral-blood CD4 cell count of more than 200 cells per cubic millimeter. RESULTS: Secondary prophylaxis was discontinued at a median CD4 cell count of 350 per cubic millimeter; the median nadir CD4 cell count had been 50 per cubic millimeter. The median duration of the increase in the CD4 cell count to more than 200 per cubic millimeter after discontinuation of secondary prophylaxis was 11 months. The median follow-up period after discontinuation of secondary prophylaxis was 13 months, yielding a total of 374 person-years of follow-up; for 355 of these person-years, CD4 cell counts remained at or above 200 per cubic millimeter. No cases of recurrent P. carinii pneumonia were diagnosed during this period; the incidence was thus 0 per 100 patient-years (99 percent confidence interval, 0 to 1.2 per 100 patient-years, on the basis of the entire follow-up period, and 0 to 1.3 per 100 patient-years, on the basis of the follow-up period during which CD4 cell counts remained at or above 200 per cubic millimeter). CONCLUSIONS: It is safe to discontinue secondary prophylaxis against P. carinii pneumonia in patients with HIV infection who have an immunologic response to highly active antiretroviral therapy.

AIDS-Related Opportunistic Infections↗
PubMed2001

The Stanley Foundation Bipolar Treatment Outcome Network. II. Demographics and illness characteristics of the first 261 patients.

BACKGROUND: Since recent NIMH Bipolar Disorder Workshops highlighted the dearth of longitudinal and controlled studies of bipolar illness, the Stanley Foundation Bipolar Network (SFBN) has recruited a large cohort of patients with bipolar disorder to begin to address these issues. This report describes the demographics and course of illness characteristics of this study population. METHODS: The first 261 outpatients to be diagnosed by the Structured Clinical Interview for DSM-IV (SCID) and complete a detailed patient and a brief clinician questionnaire are described. All patients met DSM-IV criteria for bipolar I (n=211), bipolar II (n=42), or NOS (n=5) or schizoaffective (n=3), bipolar type. Chi-square and t-tests were used to examine statistically significant associations among important demographic and descriptive items. RESULTS: The general demographic and illness characteristics were similar to those in many bipolar clinical samples and not dissimilar from those reported in epidemiological surveys. The majority of patients had been hospitalized, with almost half reporting a worsening of illness over time, and two-thirds were not asymptomatic between episodes. First treatment for patients had been delayed by an average of 10 years from illness onset (by SCID). Almost a third of patients had attempted suicide at least once, and 30% reported current suicidal ideation at study entry. A total of 62% reported moderate to severe impact of the illness on occupational functioning. Early onset bipolar illness (< or =17 years old) was associated with increased frequency of mood switches, worsening course of illness, and history of early abuse (physical, verbal, or sexual). CONCLUSION: The SFBN represents a sample of predominantly BP I patients largely recruited from the community who will be followed in detail longitudinally, participate in clinical trials, and thus help advance our understanding and treatment of this life-threatening medical disorder. While there is a broad range of illness characteristics and severity, the majority of patients have been severely impacted by their illness despite the availability of multiple conventional treatment approaches in the community. These data further underscore the need for development of new and earlier treatment interventions. LIMITATION: The SFBN population is limited by the lack of random selection and represents a cohort willing to be treated and followed intensively in academic tertiary referral centers. While its characteristics are similar to many clinical study populations, the generalizability to non-clinic populations remains uncertain.

Activities of Daily Living↗
PubMed2001

Soluble interleukin-1 receptor--reverse signaling in innate immunoregulation.

Interleukin-1 (IL-1) is one of the most important proinflammatory cytokines, regulating immunological and inflammatory processes. It induces a very efficient and self-amplifying cytokine-network. The action of IL-1 must, therefore, be under tight control. Soluble IL-1 receptor was thought to be an efficient negative regulator of the IL-1 signaling system. However, recent studies in vitro and in vivo demonstrate that soluble IL-1 receptor can act as an agonist as well, inducing intracellular signaling events. This feature of soluble IL-1 receptor adds a new level of complexity to our understanding of ligand-receptor cross-talk and cell-to-cell communication.

Adjuvants, Immunologic↗
PubMed2001

Cytokine gene expression in chronic periodontitis.

BACKGROUND: Cytokines play an important rôle in controlling inflammatory processes and tissue homeostasis. Periodontitis, as any other chronic inflammatory disease, results from a disarrangement of host factors, mainly cytokines and the initiating agent. Modulation of the cytokines is not only controlled by the host but also by infecting bacteria and their products. AIM: In the present study, we examined the cytokine mRNA expression profiles in six patients, each presenting sites affected with (1) severe progressive periodontitis, (2) chronic, but stable periodontal lesions, and (3) with healthy sites. Analysis using a quantitative RT-PCR included IFN-gamma, IL-1beta, IL-2, IL-4, IL-5, IL-6, and TNF-alpha. MATERIAL AND METHODS: 6 patients with chronic periodontitis were following treatment observed for a period of six years for local sites staying healthy, local sites with periodontal pathology but without signs of progression of attachment loss and sites with verified progression were biopsied. The biopsies were lyzed and analyzed for levels of cytokine mRNAs. RESULTS: Results revealed considerable variation not only between patients, but also between individual sites. Each patient's site has thus to be looked at as an independent entity. CONCLUSIONS: The local action of cytokines, which is heavily dependent on recruitment, interaction and activation of immunocompetent cells can explain the site-specific nature of cytokine expression. Cytokine data from individual sites together with the local clinical status and data from the literature demonstrate the complexity of periodontal disease pathogenesis. To gain insight to specific mechanisms further studies are needed.

Aged↗
PubMed2001

Inhibition of ATP-binding cassette transporter downregulates interleukin-1beta-mediated autocrine activation of human dermal fibroblasts.

Fibroblasts constitute an important source of cytokines during inflammatory processes in the skin. Interleukin-1 is a potent, pleiotropic cytokine that is induced in activated human dermal fibroblasts. Interleukin-1 further induces many inflammatory mediators, including the chemokine interleukin-8. As fibroblasts express both interleukin-1 and the interleukin-1 receptor complex, the cellular response may be enhanced by autocrine activation. Interleukin-1alpha and interleukin-1beta lack a signal peptide and are translocated at the plasma membrane using an alternative secretory pathway, which may involve ATP-binding cassette transporter proteins. We hypothesize that inhibition of this pathway prevents secretion of interleukin-1, thereby downregulating interleukin-1-dependent autocrine induction of interleukin-8. We used the ATP-binding cassette 1 transporter inhibitor glybenclamide, which has been previously shown to block interleukin-1beta secretion in human monocytes. Using enzyme-linked immunosorbent assay, we assessed the effect of glybenclamide on interleukin-8 production in human dermal fibroblasts. In interleukin-1beta-transfected human dermal fibroblasts, interleukin-8 was induced through an autocrine activity of interleukin-1beta. Glybenclamide disabled this activation loop and significantly reduced interleukin-8. In human dermal fibroblasts that were stimulated with tumor necrosis factor alpha to reach high interleukin-1 expression levels, glybenclamide similarly suppressed interleukin-8. In contrast, glybenclamide did not affect interleukin-8 production in cells stimulated with interleukin-1 only. Glybenclamide did not affect caspase-1 in fibroblasts, which was expressed as an inactive precursor form, irrespective of treatments with tumor necrosis factor alpha and/or glybenclamide. Using overexpressing, interleukin-1-transfected COS-1 cells, inhibition of interleukin-1alpha and interleukin-1beta secretion was directly demonstrated on Western blots. These results are consistent with glybenclamide preventing externalization of interleukin-1 and subsequent autocrine induction of interleukin-8 in human dermal fibroblasts. Acting through such a mechanism, ATP-binding cassette transporter inhibitors may downregulate inflammation locally.

ATP-Binding Cassette Transporters↗
PubMed2000

Natural killer cells activate human dermal fibroblasts.

Human dermal fibroblasts (HDF) undergo activation and secrete cytokines when cocultured with T cells. Here, we identify potent activators of HDF among human peripheral CD2(+)-lymphocytes. Populations with strong HDF activating capacity consisted essentially of cells with a natural killer (NK) surface marker phenotype (CD3(-), CD4(-), CD8(-), CD56(+)). Addition of these cells to HDF resulted in rapid increase of intracellular free calcium concentrations as an early rapid cell activation signal. Upregulation of mRNA encoding for the inflammatory cytokines IL-1 beta and IL-6 as well as for chemokines IL-8 and MCP-1 was detected after cells were cocultured. Elevated concentrations of IL-6 and IL-8 were found in coculture supernatants of HDF and NK-cells. Skin-homing NK cells leaving the blood-stream during an inflammatory skin reaction might therefore represent potent activators of local inflammatory cytokine and chemokine production.

CD2 Antigens↗
PubMed2000

Radiochemistry: inconvenient but indispensable

Radiochemistry has always been and still is a crucial tool in the field of radionuclide determination, both for high and low level works; this holds particularly in the case of alpha and beta emitters. Requests to the analyst are increasingly demanding in terms of performance (detection limit, reliability, accuracy, precision,...), but also of economy (cost, time,...) and of flexibility with respect to sample types. In general, chemical and radiochemical analyses consist of four main steps: sample pre-treatment including pre-concentration, dissolution and/or digestion, separation of analytes from the matrix and from each other, transformation of the separated fraction into a source suited for measurement, determination of the amount or the activity of the analytes. The required combination of sub-procedures is determined by the analytes under investigation, their absolute and relative amounts, the matrix composition and by the performance required. IRMM's Analytical Chemistry Unit started several years ago to develop, adapt and/or validate various radiochemical methods and procedures, and apply these to different measurement tasks. This paper gives an overview on recent and ongoing activities.

Journal Article↗
PubMed2000

Actinoid separations by extraction chromatography

Two separation methods based on extraction chromatography are presented: the first for the determination of Pu and Am, and the second for U and Th. These two methods are applied to (i) the determination of Pu and Am in diluted MOX samples and (ii) the analyses of Th from four standard solutions. Both of the methods gave high recoveries and showed good reproducibility for Th, Pu and Am. Special requirements for the determination of Th are discussed.

Journal Article↗
PubMed2000

Pre-concentration of actinoids from waters: a comparison of various sorbents

The first part of comparison study was based on the properties of different sorbents. These included different forms of manganese oxides, and specific organic ion-exchangers: HYPHAN and POLYORGS. In order to provide reproducible samples with moderate presence of possible interferences, spiked tap water was used for this first set of experiments. Results indicate that the sorption of Th, U, Pu and Am varies for different forms of manganese oxides. These variations are attributed to different physico-chemical properties of the oxides. HYPHAN was limited in its sorption to Th and U. The manganese oxide dissolved rapidly and the radiochemical separation procedure was quick and simple using extraction chromatography techniques. The radionuclides in the water samples were determined by ICP-MS and/or alpha spectrometry.

Journal Article↗
PubMed2000

Results from the international evaluation exercise for uranium enrichment measurements. European Safeguards Research and Development Association NDA-WG Members

An international evaluation exercise for uranium enrichment measurement was organized by the ESARDA (European Safeguards Research and Development Association) Working Group on Techniques and Standards for Non-Destructive Analysis. The aim of this exercise was to test the different methods and more particularly X- and gamma-ray spectrometry methods used in the determination of uranium enrichment. Sets of samples of different uranium enrichments prepared by IRMM (Institute for Reference Materials and Measurements) and BNFL (British Nuclear Fuels) were measured by 15 participants in the IRMM laboratories. A description of this exercise is given here and the final results with their uncertainties are compared to the reference values obtained from mass spectrometry measurements. The main conclusions from this exercise are proposed; in particular, it appears necessary to improve the nuclear data used in the spectral modeling of the XKalpha region.

Journal Article↗
PubMed1999

Chemokine gene expression in human oral mucosa.

In order to gain further understanding of the role of chemokines in healthy oral mucosa, we analyzed mRNA expression of the alpha (CXC)-family chemokines IL-8 and GROgamma as well as of the beta (CC)-family chemokines MIP-1alpha, MIP-1beta and MCP-1 in twenty young and healthy subjects with good oral hygiene. Twenty biopsies were taken from clinically healthy oral mucosa before surgical removal of impacted wisdom teeth. In addition, five biopsies from patients presenting with specific oral lesions were studied. RNA was purified, quantitated and utilized as substrate for competitive reverse transcription-polymerase chain reaction (RT-PCR). In healthy tissue, IL-8 and MCP-1 mRNA was constitutively expressed in all biopsies, whereas GROgamma, MIP-1alpha, and MIP-1beta were significantly lower. These findings suggest that IL8 and MCP-1 play a significant role in oral tissue homeostasis. The few samples from pathological conditions encourage exploring diseased tissue in more detail.

Adolescent↗